Pii: s0022-3476(99)70053-3

LLactobacillus GG in the prevention of antibiotic-
associated diarrhea in childrenJon A. Vanderhoof, MD, David B. Whitney, MD, Dean L. Antonson, MD, Terri L. Hanner, RN,James V. Lupo, PhD, and Rosemary J. Young, RN, MSObjective: The objective of this study was to determine the efficacy of Lac-
tion.3,4 Disruption of the microbial flora
tobacillus casei sps. rhamnosus (Lactobacillus GG) (LGG) in reducing the inci-
may result in the overgrowth of patho-genic organisms such as Clostridium dif-
dence of antibiotic-associated diarrhea when coadministered with an oral
ficile or may disturb the metabolism of
antibiotic in children with acute infectious disorders.Study design: Two hundred two children between 6 months and 10 years
tion of osmotically active particles.
of age were enrolled; 188 completed all phases of the protocol. LGG, 1 ×1010 – 2 × 1010 colony forming units per day, or comparable placebo wasadministered in a double-blind randomized trial to children receiving oral
See editorial, p. 535.
antibiotic therapy in an outpatient setting. The primary caregiver was ques-tioned every 3 days regarding the incidence of gastrointestinal symptoms,
predominantly stool frequency and consistency, through telephone contact
gut microflora in conditions where dis-turbances of normal bacterial flora re-
Results: Twenty-five placebo-treated but only 7 LGG-treated patients had
diarrhea as defined by liquid stools numbering 2 or greater per day. Lacto-bacillus GG overall significantly reduced stool frequency and increased stool
consistency during antibiotic therapy by the tenth day compared with the
Conclusion: Lactobacillus GG reduces the incidence of antibiotic-associated
diarrhea in children treated with oral antibiotics for common childhood in-
their inability to survive in gastric and
bile secretions, inability to colonize thegastrointestinal tract, and ineffectivebinding to intestinal epithelial cells.7-9
Lactobacillus casei sps. rhamnosus (Lacto-
in pediatrics, most often for a variety of
bacillus GG) has been shown to do all 3
minor infections of the respiratory tract,
antibiotics, especially those with a rela-
flora in the gastrointestinal tract. More
ic-associated diarrhea in children ranges
suitable probiotic in this situation.10-12Consequently, we elected to initiate a
From the Department of Pediatrics, University of Nebraska, Omaha; Black Hills Pediatrics, Children’s Hospital,Rapid City, South Dakota; and Departments of Pediatrics and Psychology, Creighton University, Omaha, Nebraska.
Supported by a grant from CAG Nutrition, a division of ConAgra, Inc of Omaha, Nebraska. Dr
of Lactobacillus GG with antibiotics
Vanderhoof serves as a consultant for ConAgra.
Submitted for publication Dec 31, 1998; revision received Mar 23, 1999; accepted May 18, 1999.
of minor infections to assess the effica-
Reprint requests: Jon A. Vanderhoof, MD, 985160 NE Medical Center, Omaha, NE 68198-5160.9/21/101359
.80 power), 202 children between theages of 6 months and 10 years were re-cruited from a busy private primarycare pediatric practice for participationin this study. The population base waslargely representative of a middle class,Midwestern city (population 50,000).Image available in print only
However, this practice receives manyrural and minority (Native-American)referrals. All were being evaluatedduring the month of September forsymptoms of acute infection of theupper or lower respiratory tract, theurinary tract, soft tissues, or skin. Onlychildren who were prescribed a 10-daycourse of antibiotics were included.Fig 1. Line drawings depicting stool consistency and given numeric value. From Young RJ, Beerman
LE,Vanderhoof JE. Increasing oral fluids in chronic constipation in children. Gastroenterol Nurs1998;21:156-61. Reprinted with permission.
rious acute infection, or diarrhea at thetime of antibiotic initiation were ex-cluded. Once the decision was made to
allowed during the course of the study.
ther LGG or a placebo in capsule form.
score based on a visual analog scale.
were assessed and graded numerically.
complete the study, primarily becauseof antibiotic noncompliance or inabilityof the investigators to contact the pri-mary caregiver at the assigned follow-up time. None of the participants failedto complete the 10-day course of antibi-otics because of a change in stool con-sistency or frequency. There were nofailures resulting from untoward effectsof either LGG or placebo. Both activeand placebo groups were similar forage distribution, sex, and type of antibi-otics, and all who completed the studyhad no difficulty consuming the pre-scribed amount. The most common an-tibiotics prescribed, the reason for theiruse, and other patient characteristicsare listed in Table I. Compliance wasmeasured by capsule counting at the
Fig 2. Mean stool consistency per day ± SEM for each observation period for both active andplacebo groups is shown. Active is displayed in solid bars and placebo in open bars. By day 10, signifi-
cant difference in stool consistency was observed (P < .02).
diarrhea was defined as the presence ofat least 2 liquid stools per day on atleast 2 observation periods during thecourse of this study. With this defini-tion 25 (26%) patients who receivedplacebo but only 7 (8%) who receivedLGG had diarrhea during antibioticadministration. The mean duration ofdiarrhea was 4.70 days in the LGGgroup and 5.88 days in the placebogroup (P = .05). Mean stool consisten-cy scores at each observation point forthe active and placebo groups areshown in Fig 2. There was a gradualtrend toward decreasing stool consis-tency over time, with the active groupdiffering significantly from the placebogroup by the tenth day (P < .02). Astool consistency score of <4 on eitherday 7 or day 10 was significantly more
Fig 3. Mean number of stools per day ± SEM for each observation period for both active and
placebo groups is shown. Active is displayed in solid bars and placebo in open bars. By day 10, signifi-cant difference in mean stool frequency was observed (P < .02).
than in the LGG-treated group; 48% ofthe children treated with placebo had astool consistency score of <4 during the
score of <4 (P < .001). Mean stool fre-
pairwise comparisons were performed.
the stool consistency score of <4 on ei-
the placebo group (P < .02).Clostridium difficile colonization was
Table I. Study demographics
child with significant diarrhea at thebeginning of the study was enrolled,
solve shortly after the end of antibiotic
DISCUSSION
health benefits including ameliorationor prevention of a specific diseasestate.6 These organisms generally en-
Table II. Antibiotic sensitivity of Lacto-
ing Clostridium difficile diarrhea, having
as probiotics are destroyed in the acidic
Clostridium difficile-associated diarrhea
MIC, Minimum inhibitory concentration.
after oral administration is ceased.12,18
at all.9 Ideally, final verification of the
its probiotic capabilities. It was initially
use as a probiotic in any specific condi-
classified as a Lactobacillus rhamnosus,
subsequently as a Lactobacillus casei,
classic example of the deleterious effect
flora both quantitatively and qualitative-
ly. Twenty percent to 40% of all children
EFERENCES
1. Bartlett JG. Antibiotic-associated di-
Lactobacillus strain (Lactobacilluscasei sp strain GG) promotes recovery
arrhea. Clin Inf Dis 1992;15:573-81.Clostridium difficile to antibiotic-associ-
dicting pressure sore risk. Nurs Res1987;36:205-10.
18. Saxelin M, Pessi T, Salminen S. Fecal
ampicillin. Gastroenterology 1988;94:928-32.
antibiotic as a result of frustration over
prebiotics. J Nutr 1994;125:1401-12.
al. Effect of Lactobacillus GG yoghurt in
Hart CA. Lactobacillus GG and acute di-arrhoea in young children in the trop-
populations. Int J Food Microbiol1997;35:1-27.
subject of antibiotic resistance to lacto-
Singer C. Efficacy of Lactobacillus GG
as a diarrheal preventative in travelers.
Smith CT. “Probiotic” remedies arenot what they seem. Br Med J 1996;
has also demonstrated that L rhamnosus
Salminen S. Effect of Lactobacillus
23. Gorbach, SL, Chang TW, Goldin BR.rhamnosus strain GG (ATCC 51303) on
Successful treatment of relapsingClostridium difficile colitis with Lacto-
the growth of Streptococcus dobrinus invitro. Eur J Oral Sci 1995;103:253-8.bacillus GG. Lancet 1987;2:1519.
rent Clostridium difficile colitis with Lac-Lactobacillus rhamnosus GG from human
tobacillus GG. J Pediatr GastroenterolNutr 1995;21:224-6.
26. Salminen S, Von Wright A. Lactic acid
cluded the use of parental interview as a
species. J Food Prot 1998;61:1636-43.
28. Tynkkynen S, Singh KV, Varmanen P.
acute disease or antibiotic type was also
Vancomycin resistance factor of Lacto-
tana S, Cuevas L, Hart CA. Lactobacil-bacillus rhamnosus GG in relationship to
not controlled, but statistical analysis of
lus GG promotes recovery from acute
tween them for any of the variables.

Eat More : seen in menopausal women, and as they are associated t Plant-based foods, especially fresh fruits and with an increased risk for cardiovascular disease, it may be vegetables such as cabbage family vegetables – appropriate to ensure optimal intake of these nutrients either broccoli, cabbage, brussel sprouts, cauliflower, bok choy, Chinese broccoli, broccolini, Garlic and oni

Leukemia Definition: A cancer involving the blood forming cells Acute leukemia is the most common malignancy in children. It is due to a clonal proliferation of hematopoietic cells (usually white blood cells). In leukemia, abnormal immature white cells increase greatly and invade other tissues and organs. These white cells are not able to function at their normal task of fighting disease whic